Beta-dihydro-inylamine and the acid addition salts thereof



Patented Sept. 27, M49

B-DIHYDBM)-II lYL1 lll IINE AND THE ACID ADDITION SALTS THEREOF Moses Wolf Goldberg, Upper Montclair, and Sidney Teitel, Nutley, N. J., assignors to H011"- mann-La Roche Inc., Nutley, N. 3., a corporation of New Jersey No Drawing. Application March 9, 1948, Serial No. 13,953

4 Claims. (01. 260501) I 1 2 The present invention relates to a new amine sure are not critical and can therefore be varied and its acid addition salts, and to a process for Within a wide range, and instead of methanol, preparing th e min other solvents such as ethanol, isopropanol, ethyl More particularly the invention relates to the acetate and the like, can also be employed. new compound 1 methyl-S-(2,6,6-trimethyl-l- 5 1-methy1-3-(2,6,6 trimethyl-l-cyclohexen 1- cyclohexen-l-yl) -propy1amine and its salts with yD-propylamine can be converted to'its hydroinorganic and organic acids, for example, the chloride, for example, by adding aqueous hydrohydrochloric acid, the hydrobromic acid and the chloric acid directly to the amine suspended in benzoic acid salts. The new amine and its salts water. The precipitated salt, after recrystallizaserve as valuable intermediates for the production from water, melts with decomposition at tion of new compounds, in particular for the 2 5 2 C. The hydrob Om de m y e Similarly production of new insoluble penicillin salts of prepared and melts with decomposition at 222- high therapeutic activity, which form the sub- 223 C. after recrystallization from acetonitrile. ject of our application Serial No. 13,954, filed The benzoate may be prepared by neutralizing March 9, 1948, now U. S. Patent 2,843,382. 5 an alcoholic solution of the amine with an alco- The structure of the new amine is related to holic solution of benzoic acid. The oil obtained that of dihydro-e-ionone, and can be represented after removal of the alcohol is crystallized from by the following formula; ether-acetonitrile. The benzoate melts at 91- HaC CH3 92 C' G Example 2 Twenty grams of dihydro-p-ionone dissolved |OOHZ CH2CH NH in 100 cc. of ethanol saturated with ammonia H2O CH3 H3 are catalytically hydrogenated in the presence a 5 of 4 grams of Fancy nickel at 75 C. and 2,000 ounds per square inch hydrogen pressure for The new amine can be prepared most advanp tageously and in excellent yield by direct catar about 24 hours. The reaction mixture is worked lytic hydrogenation of fi-ionone in the presence 2% fi fig jg g z fgfigfiggjiggfi igggfif of ammonia and a hydrogenation catalyst, such 1) r0 1 mi 6 6 3 t 108 C t 7 kel latinum or palladium catalyst. Of y mg as a me p and 1dent1ca1 with the product described in Exthe two double bonds present 1n ,B-lOIlOIle, the

one adjacent to the keto-group is thus reduced g h and the keto-group converted into an amino- 1 group. However, the new amine can also be A compound selected group obtained in equally good yields in two steps, by 5 slstmg of f first reducing c-ionone to the known dihydroii ii' 'propylamme and the and addltlon fl-ionone, for example, by catalytic hydrogenas ereo tion, and then reacting the latter with hydro- 1 i tnmefihyll'cyclohexen' gen and ammonia in the presence of a hydro- )"prpy1amme hydrocmonde' genation catalyst, in the same way as described 40 'a' tnmeFhyll'cyclohexen for fiqonona 1-yl)-propylam1ne hydrobromide.

The following examples will serve to illustrate tnmethylbcyclohexen the invention: l-yl) -propylam1ne benzoate.

Example 1 MOSES WOLF GOLDBERG.

SIDNEY TEITEL.

Four hundred grams of p-ionone, dissolved in 900 cc. of a 17 per cent solililtion of ammonia in REFERENCES CITED methanol, are ca aly ically ydrogenated in the presence of about 30 grams of Haney nickel at The following references are of record in the 150 C. and 2,000 pounds per square inch hydrofile of thls patent gen pressure for about 24. hours. The catalyst is UNITED STATES PATENTS then filtered off and the methanol solution concentrated. The residual liquid is fractionated figi fiig 3 3 by vacuum distillation at 5 mm. mercury pres- 1 989325 Lommel g Jan 1935 sure. A yield of at least 335 grams of l-methyl- 2045574 Adkins June 1936 3-(2,6,6-trimethyl-1 cyclohexen- 1-y1)-propyl- 2:278:123 Heyn Mar 311942 amine is obtained. The boiling point of the new 2367546 Unyot 1945 amine is 106l08 c. at 5 mm. and 125-126 c. at

13 m OTHER REFERENCES In carrying out the preparation of the new Gunn et al., J.-Physiol., (1940), V01. 97, page amine, the hydrogenation temperature and pres- 

